Asthma is a disease characterized by reversible airflow obstruction and bronchial inflammation. There is considerable evidence in human and murine models of asthma that CD4 T cells and in particular IL-4 and IL-5 secreting Th2 cells are associated with the characteristic airway response. The goals of this proposal are 1) to understand the role of committed Th1 and Th2 effector CD4 T cells in eliciting airway inflammation and bronchial hyperresponsiveness focussing on characterizing the unique pathology induced by each type of effector T cell and 2) to determine if the interaction between Th1 and Th2 cells in the airway is synergistic or antagonistic in the induction of airway events. To understand how the pathology associated with asthma can be elicited and regulated by activated CD4 T cells, we will take advantage of an established cell transfer system in which antigen-specific, committed Th1 cells, Th2 cells or both, derived from mice transgenic for a known T cell receptor, are transferred into naive mice and are recruited and activated in the airway by inhaled antigen. The role of Th1 and Th2 effector cells in inhibiting or exacerbating airway inflammation and hyperresponsiveness will be examined by 1) characterizing the effect of transferring either primed Th1 or Th2 CD4 effector T cells on airway events, 2) determining the role of Th2/Th1 cytokines and cytokine responsive cells in the generation of airway inflammation and AHR using cytokine/cytokine receptor deficient mice, and 3) determining the effect of Th1: Th2 interaction of the airway microenvironment on modulating the airway response elicited by a particular subset of CD4 T cell. From these studies we hope to gain an understanding of the role of Th1 and Th2 cells in eliciting a pathology characteristic of human asthma and to investigate methods to abrogate an ongoing, committed CD4 effector T cell response.